Prevalence of d3-GHR homozygotes in relation to age groups in: (A) Ashkenazi Jew (AJ) (female and male of control and centenarian, n = 344) combined and (A1) split by gender (196 males and 148 females), (B) OOA 152 males, (C) 61 white males of the CHS, and (D) 61 French white males and (E) mega analysis of the four cohorts (470 males). In each of the cohorts, there is increased prevalence of the homozygote d3-GHR (*P < 0.05 for the trend).

Fig. 3Distribution of GHBP (in pM) among the centenarians (95F and 102M), their offspring (113F and 110M), and controls (53F and 94M), all of whom are of Ashkenazi (AJ) descent, in recessive model [homozygous GHR deletion of exon 3 (d3-GHR) versus heterozygote (Het) and WT combined], adjusted for gender and age (*P < 0.05).

(A) In vitro effect of GH stimulation (100 ng/ml) on proliferation of transformed lymphocytes from male AJ centenarians. In the basal state [serum-free (SF)], lymphocytes from d3-GHR homozygous subjects have reduced proliferation rates; however, in the presence of GH, there is enhanced responsiveness and overall higher growth rates. This is compatible with reports in humans showing an increased responsiveness to GH only in studies that use high doses of GH. AU, arbitrary units. (B) Phosphorylation of ERK in homozygous WT and d3-GHR transformed lymphocytes from male AJ centenarians. Lymphocytes from d3-GHR homozygotes displayed significantly lower pERK levels under serum-free conditions but higher activation of ERK in response to GH treatment (100 ng/ml), compared to WT (fl/fl) carriers (**P < 0.01).